反应详情

To a mechanically stirred solution of 1.5 g of the above 6,8-dichloro-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one in 150 mL of glacial acetic acid at 60° C. was added 25 g of zinc dust. To this suspension was then added dropwise a solution of 35 mL of concentrated hydrochloric acid in 50 mL of glacial acetic acid in 20 minutes. After the addition was complete, the mixture was stirred for an additional 10 minutes. Then the unreacted zinc was filtered off (Caution!, Pyrophoric!), washed with 4×30 mL of glacial acetic acid and the filtrate was concentrated in vacuo. To the residue was added 80 mL of 20% aqueous sodium hydroxide and the product was extracted with tetrahydrofuran (3 times 150 mL). The organic extract was concentrated in vacuo and the residue was distributed between 100 mL of chloroform and 25 mL of water. The aqueous layer was extracted with 2×25 mL of chloroform. The combined extract was dried with anhydrous potassium carbonate, filtered, concentrated in vacuo, and flash chromatographed on silica gel, using 10:1 chloroform-methanol as eluent. The base was treated with 1 equivalent of 4N HCl in 50 mL absolute ethanol, concentrated in vacuo, redissolved in 50 mL absolute EtOH, concentrated, repeated again. Then the white solid was recrystallized from absolute EtOH-EtOAc, giving after drying in vacuo 0.8 g of 6,8-dichloro-1,2,3,9-tetrahydropyrrolo[2,1-b]-quinazoline hydrochloride in the form of white crystals, m.p. 305° C.-310° C. (dec.).

1. additionAfter the addition
2. filtrationThen the unreacted zinc was filtered off (Caution!, Pyrophoric!)
3. washwashed with 4×30 mL of glacial acetic acid
4. concentrationthe filtrate was concentrated in vacuo
5. additionTo the residue was added 80 mL of 20% aqueous sodium hydroxide
6. extractionthe product was extracted with tetrahydrofuran (3 times 150 mL)
7. extractionThe organic extract
8. concentrationwas concentrated in vacuo
9. extractionThe aqueous layer was extracted with 2×25 mL of chloroform
10. extractionThe combined extract
11. dry with materialwas dried with anhydrous potassium carbonate
12. filtrationfiltered
13. concentrationconcentrated in vacuo, and flash
14. customchromatographed on silica gel
15. concentrationconcentrated in vacuo
16. dissolutionredissolved in 50 mL absolute EtOH
17. concentrationconcentrated
18. customThen the white solid was recrystallized from absolute EtOH-EtOAc
19. customgiving
20. dry with materialafter drying in vacuo 0.8 g of 6,8-dichloro-1,2,3,9-tetrahydropyrrolo[2,1-b]-quinazoline hydrochloride in the form of white crystals, m.p. 305° C.-310° C. (dec.)